Calcium (Ca2+) is a major regulator of cardiac contractility. When a myocyte is depolarized by an action potential, Ca2+ enters the cell primarily via L-type voltage-gated Ca2+ channels with a smaller contribution occurring via the reverse mode of the sodium-calcium exchanger (NCX) channels. This Ca2+ influx in the cytosol acts to trigger a subsequent release of Ca2+ stored in the sarcoplasmic reticulum through Ca2+-release channels ultimately leading to myocardial contraction
The efflux of Ca2+ occurs via the forward mode of the NCX and via the plasma membrane Ca2+-ATPase mechanism. The net Ca2+ flux through the NCX occurs in the outward direction. Previous studies estimating the relative contributions to Ca2+ efflux have shown that the NCX is the dominant mechanism with 9-32% of the efflux occurring from non-NCX mechanisms in rats and 19% in mice.
Alterations in myocyte Ca2+ handling are prevalent in the dysfunctional characteristics of a failing heart. Moreover, the NCX inhibitor SEA0400 has been shown to therapeutically reduce myocardial injury due to abnormal intracellular Ca2+ handling. While this inhibitor is useful in treating abnormal intracellular Ca2+ handling, it would be useful to monitor Ca2+ influx and efflux in vivo; however, no techniques exist to either directly or indirectly observe in vivo intracellular Ca2+ fluctuations across the plasma membrane.